I assume that you meant that the table should have many records with null value in this column, but the rest of the values should be unique. If I'm correct then you can try and use filtered unique index on that table (the filter would be of course on the null value).

It's easier with varchar, nvarchar, and varbinary since it's generally not too difficult to convert the primary key to one of those types; other column types could be an issue.And there's another complication - you need some way of ensuring that the value you convery the primary key into when the column in question has a null never clashes with some other value in that column, which may turn out to be nontrivial.